Does FSH signaling have a gender?

FSH is the main endocrine control of mammalian reproduction. FSH triggers somatic cells of the gonads which support germ cells metabolically, i.e. Sertoli cells of the seminiferous tubules, and granulosa cells harboring the oocyte, within the ovarian follicle. FSH leads to similar biological responses in both cell types since it stimulates proliferation and differentiation, according to the developmental stage. However, FSH receptor knock-out female mice are infertile, unlike male mice. Hence, FSH is not equally important in both sexes. Nevertheless, does FSH induce distinct signalling mechanisms in its target cells ? Here, we compare the signalling mechanisms induced by FSH in ovarian and testicular physiology.     

Sensitivity and responses of diatoms to climate warming in lakes heavily influenced by humans

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DGKI Methylation Status Modulates the Prognostic Value of MGMT in Glioblastoma Patients Treated with Combined Radio-Chemotherapy with Temozolomide

Background

Consistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status.

Methods

399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2.

Results

The nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram.

Conclusions

Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.     

Molecular basis for the differential interaction of plant mitochondrial VDAC proteins with tRNAs

In plants, the voltage-dependent anion-selective channel (VDAC) is a major component of a pathway involved in transfer RNA (tRNA) translocation through the mitochondrial outer membrane. However, the way in which VDAC proteins interact with tRNAs is still unknown. Potato mitochondria contain two major mitochondrial VDAC proteins, VDAC34 and VDAC36. These two proteins, composed of a N-terminal α-helix and of 19 β-strands forming a β-barrel structure, share 75% sequence identity. Here, using both northwestern and gel shift experiments, we report that these two proteins interact differentially with nucleic acids. VDAC34 binds more efficiently with tRNAs or other nucleic acids than VDAC36. To further identify specific features and critical amino acids required for tRNA binding, 21 VDAC34 mutants were constructed and analyzed by northwestern. This allowed us to show that the β-barrel structure of VDAC34 and the first 50 amino acids that contain the α-helix are essential for RNA binding. Altogether the work shows that during evolution, plant mitochondrial VDAC proteins have diverged so as to interact differentially with nucleic acids, and this may reflect their involvement in various specialized biological functions.     

Regulation of Hepatic Drug Transporter Activity and Expression by Organochlorine Pesticides

Organochlorine (OC) pesticides constitute a major class of persistent and toxic organic pollutants, known to modulate drug‐detoxifying enzymes. In the present study, OCs were demonstrated to also alter the activity and expression of human hepatic drug transporters. Activity of the sinusoidal influx transporter OCT1 (organic cation transporter 1) was thus inhibited by endosulfan, chlordane, heptachlor, lindane, and dieldrine, but not by dichlorodiphenyltrichloroethane isomers, whereas those of the canalicular efflux pumps MRP2 (multidrug resistance‐associated protein 2) and BCRP (breast cancer resistance protein) were blocked by endosulfan, chlordane, heptachlor, and chlordecone; this latter OC additionally inhibited the multidrug resistance gene 1 (MDR1)/P‐glycoprotein (P‐gp) activity. OCs, except endosulfan, were next found to induce MDR1/P‐gp and MRP2 mRNA expressions in hepatoma HepaRG cells; some of them also upregulated BCRP. By contrast, expression of sinusoidal transporters was not impaired (organic anion‐transporting polypeptide (OATP) 1B1 and OATP2B1) or was downregulated (sodium taurocholate co‐transporting polypeptide (NTCP) and OCT1). Such regulations of drug transporter activity and expression, depending on the respective nature of OCs and transporters, may contribute to the toxicity of OC pesticides.     

Impact of Osteopathic Treatment on Pain in Adult Patients with Cystic Fibrosis – A Pilot Randomized Controlled Study

Background

Pain is a common complication in patients with cystic fibrosis (CF) and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT) on pain in adults with CF.

Methods

A pilot multicenter randomized controlled trial was conducted with three parallel arms: OMT (group A, 16 patients), sham OMT (sham treatment, group B, 8 patients) and no treatment (group C, 8 patients). Medical investigators and patients were double-blind to treatment for groups A and B, who received OMT or sham OMT monthly for 6 months. Pain was rated as a composite of its intensity and duration over the previous month. The evolution of chest/back pain after 6 months was compared between group A and groups B+C combined (control group). The evolution of cervical pain, headache and quality of life (QOL) were similarly evaluated.

Results

There was no statistically significant difference between the treatment and control groups in the decrease of chest/back pain (difference = −2.20 IC95% [−4.81; 0.42], p = 0.098); also, group A did not differ from group B. However, chest/back pain decreased more in groups A (p = 0.002) and B (p = 0.006) than in group C. Cervical pain, headache and QOL scores did not differ between the treatment and control groups.

Conclusion

This pilot study demonstrated the feasibility of evaluating the efficacy of OMT to treat the pain of patients with CF. The lack of difference between the group treated with OMT and the control group may be due to the small number of patients included in this trial, which also precludes any definitive conclusion about the greater decrease of pain in patients receiving OMT or sham OMT than in those with no intervention.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01293019","term_id":"NCT01293019"}}NCT01293019     

A Double-Blind,Placebo-Controlled Study on the Effects of Lutein and Zeaxanthin on Neural Processing Speed and Efficiency

Lutein and zeaxanthin are major carotenoids in the eye but are also found in post-receptoral visual pathways. It has been hypothesized that these pigments influence the processing of visual signals within and post-retina, and that increasing lutein and zeaxanthin levels within the visual system will lead to increased visual processing speeds. To test this, we measured macular pigment density (as a biomarker of lutein and zeaxanthin levels in brain), critical flicker fusion (CFF) thresholds, and visual motor reaction time in young healthy subjects (n = 92). Changes in these outcome variables were also assessed after four months of supplementation with either placebo (n = 10), zeaxanthin only (20 mg/day; n = 29) or a mixed formulation containing 26 mg/day zeaxanthin, 8 mg/day lutein, and 190 mg/day mixed omega-3 fatty acids (n = 25). Significant correlations were found between retinal lutein and zeaxanthin (macular pigment) and CFF thresholds (p<0.01) and visual motor performance (overall p<0.01). Supplementation with zeaxanthin and the mixed formulation (considered together) produced significant (p<0.01) increases in CFF thresholds (∼12%) and visual motor reaction time (∼10%) compared to placebo. In general, increasing macular pigment density through supplementation (average increase of about 0.09 log units) resulted in significant improvements in visual processing speed, even when testing young, healthy individuals who tend to be at peak efficiency.